This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (A) Objectives. Chemical modulation and inhibition of oncogene regulation and expression is a promising therapeutic approach to the treatment of many cancers. To advance this approach, our goal is the identification, optimization and characterization of small molecule inhibitors and stabilizers of protein-protein interactions affecting the Myc network and the PI 3-kinase (PI3K) pathway. Protein-protein interactions remain challenging targets for small molecules;progress in this area will open new opportunities for drug development. This collaboration will rely upon several advances in the AutoDock suite of programs that enable the discovery of drugable sites to modulate protein-protein interactions, and which factor in dynamic characteristics of these sites.